Xu, Qingping, Abdubeck, Polat, Chen, Connie, Feuerhelm, Julie, Grant, Joanna, Klock, Heath, Knuth, Mark, Nigoghossian, Edward, Okach, Linda, Puckett, Christina, Wooten, Tiffany, Zhou, Jiadong, Lesley, Scott and Stolz, Barbara (2010) GNF ID 100604: Crystal structure of a membrane attack complex/perforin (MACPF) family protein from a human gut symbiont Bacteroides thetaiotaomicron. Acta F.

Abstract

Membrane attack complex/perforin (MACPF) proteins are transmembrane pore-forming
proteins that are important in both human immunity and virulence of pathogens. Bacterial MACPFs
are found in diverse bacterial species, including most human gut-associated Bacteroides. We
determined the crystal structure of a bacterial MACPF domain containing protein BT_3439 (Bth-
MACPF) from Bacteroides thetaiotaomicron, a predominant member of mammalian intestinal
microbiota. Bth-MACPF contains a membrane attack complex/perforin (MACPF) domain, and two
novel C-terminal domains that resemble ribonuclease H and interleukin 8 respectively. However, the
entire protein adopts a flat, crescent shape characteristic of MACPF proteins, which may be
important for oligomerization. This Bth-MACPF structure supplements knowledge of MACPF
proteins obtained previously from two other MACPF structures. Genomic context analysis infers
that Bth-MACPF may be involved in a novel protein transport or nutrient uptake system, suggesting
the potential importance of these MACPF proteins of eukaryotic origin in the adaption of
commensal bacteria to the host environment.

Item Type:	Article
Additional Information:	grant requirement B. Stolz is NOT an author -- NVS contact person for GNF manuscript approval. This manuscript shall NOT be copied to the OAK internet.
Keywords:	MACPF, Membrane attack complex, Perforin, transmembrane pores, pathogenesis
Date Deposited:	13 Oct 2015 13:16
Last Modified:	13 Oct 2015 13:16
URI:	https://oak.novartis.com/id/eprint/3111